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Study on carbon monoxide toxicity independent of hypoxia

不依赖缺氧的一氧化碳毒性研究

基本信息

批准号：
15590590
负责人：
HARA Shuichi
金额：
$ 2.24万
依托单位：
Tokyo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

1. Carbon monoxide (CO) poisoning caused by CO exposure at 3000 ppm for 40 min stimulated hydroxyl radical (・OH) generation in rat striatum.(1) The CO-induced ・OH generation was suppressed by a voltage-dependent Na^+ channel blocker, tetrodotoxin (TTX).(2) CO poisoning increased the extracellular glutamate (Glu) level, but Glu receptor antagonists (MK-801 and NBQX) had no effect on the ・OH generation.(3) α-Methyl-p-tyrosine, clorgyline (Inhibitors of DA synthesis and oxidative metabolism, respectively) and dexamethazone 21-phosphate (a phospholipase A2 inhibitor) had no effect on the CO-induced ・OH generation.(4) Nitric oxide (NO) synthase inhibitors and an NO precursor, L-arginine (L-Arg), and its enantiomer, D-Arg, had complex effects on the CO-induced ・OH generation. (This might be at least partly due to the nature of the striatum that may have a low ability to enhance NO production by utilising exogenous L-Arg.)(5) The CO-induced ・OH generation was more slowly induced by the CO poisoning in the absence of extracellular Cat than in the presence of extracellular Ca^<2+>. The ・OH generation in the absence of extracellular Ca^<2+> was suppressed by dantrolene (an inhibitor of Ca^<2+> release from sarcoplasmic reticulum).(6) Hypoxic hypoxia (HH; 5% O_2 for 40 min) stimulated ・OH generation in the striatum, though more wearly than the CO poisoning.2. CO (3000 ppm for 40 min) and HH (5% O_2 for 40 min) induced similar changes in O_2 contents and oxyhemoglobin levels, but not pO_2, in arterial blood and extracellular amino acids (Glu, taurine and alanine), the blood flow and pO_2 in the striatum.

1. 3000 ppm一氧化碳（CO）染毒40 min，可刺激大鼠纹状体产生羟自由基（·OH）。(1)CO诱导的·OH产生可被电压依赖性Na^+通道阻断剂河豚毒素（TTX）抑制。(2)CO中毒引起细胞外谷氨酸（Glu）水平升高，但Glu受体拮抗剂MK-801和NBQX对·OH的产生无影响。(3)α-甲基-p-酪氨酸、氯吉兰（分别为DA合成和氧化代谢抑制剂）和地塞米松21-磷酸（磷脂酶A2抑制剂）对CO诱导的·OH产生没有影响。(4)一氧化氮（NO）合酶抑制剂和NO前体L-精氨酸（L-Arg）及其对映体D-Arg对CO诱导的·OH产生具有复杂的影响。(This可能至少部分是由于纹状体的性质，其可能具有通过利用外源性L-Arg增强NO产生的低能力。(5)在细胞外Ca^<2+>存在的情况下，细胞外Cat不存在时，CO中毒诱导的·OH产生比细胞外Ca^<2+>存在时慢。在细胞外Ca^2+缺乏的情况下，羟自由基的产生被丹曲林（一种肌浆网Ca^2+释放的抑制剂）抑制。(6)低氧（HH; 5%O_2，40 min）刺激纹状体产生·OH，但比CO中毒更持久. CO（3000 ppm，40 min）和HH（5%O_2，40 min）引起动脉血中O_2含量和氧合血红蛋白水平的变化相似，但对纹状体细胞外氨基酸（Glu、牛磺酸和丙氨酸）、血流量和pO_2无影响。